The Effctive Of P38MAPK In Cardioprotection Of Isoflurane Postconditioning On Ischemia/Reperfusion Injury In Rat Hearts

Objective: The study is to investigate the role of p38 MAPK in protective effects of isoflurane postconditioning on myocardium ischemic/reperfusion injury in rat.Methods: Sixty adult male SD rats were randomly divided into five groups(12 each):Sham-operated group(Group C),ischemia/reperfusion group(Group IR),isoflurane postconditioning group(Group IPO),p38 MAPK inhibitor group(Group S),isoflurane postconditioning and p38 MAPK inhibitor group(Group IPOS).Each group respectively for the following processing: In group C,left anterior descending coronary artery was thread without other treatment,maintain 150min;In group IR,the heart was ligated for 30 min followed by 2h reperfusion;In group IPO,the rats were inhaled 1.0 MAC isoflurane 30 min at the same time with reperfusion,the rest with group IR;in Group S,tail vein injection of SB203580 1.5mg/kg before ligate the heart,the rest with group IR;in Group IPOS,processing method is a combination of group IPO and S.The change of ECG and myocardial color as a marker of ischemia reperfusion success.Blood samples were taken from abdominal artery at the end of reperfusion,then immediately cut off the heart at its bottom.Blood samples used to detect inflammatory cytokines IL-6 and TNF –?by ELISA.Each group of myocardial specimens for two kinds of processing:Eight of them were used for Western blot and RT-PCR detection p38 MAPK protein and m RNA expression,and caspase-3 protein expression;The rest of the four used for HE stain to observe myocardial structure and measure myocardial infarction size under light microscopy.Results: Compared with Group IR,The expression of IL-6 and TNF-? in the rest of the groups were significantly lower(P<0.01);compared with Group IPOS,the expression of IL-6 and TNF-? in Group IPO and S were significantly higher(P<0.01);Compared with group IPO,the expession of IL-6 and TNF-? in Group S were significantly lower(P<0.01);The expression of IL-6 and TNF-? in Group IPOS was the lowest.Compared with group IR,the expression of Caspase-3 in the rest of the groups were significantly lower(P<0.01);compared with Group IPOS,the expession of Caspase-3 in Group IPO and S were significantly higher(P<0.01);there was no significant difference between Group IPO and S.Compared with Group IR,the infarct size in other experimental groups were significantly reduced(P<0.01);Compared with Group IPOS,the infarct size in Group IPO and S was significantly increased(P<0.01);Compared with Group IPO,the infarct size in Group S was significantly reduced(P<0.01).Under the light microscope,pathology morphology of myocardial in Group C almost normal;group IPO?group S and IPOS pathology of myocardial damage reduced comparing with that in group IR;and compared with group IPO and S,the degree of myocardial damage in IPOS group relieved.Compared with Group IR,the expression of p38 MAPK m RNA and protein in the rest of the groups were significantly lower(P<0.01);compared with Group IPOS,the expression of p38 MAPK m RNA and protein in Group IPO and S were significantly higher(P<0.01);compared with Group IPO,p38 MAPK m RNA and protein expression in Group S were significantly lower(P<0.01).Conclusion: The activation of p38 MAPK can lead to aggravation of myocardial ischemia reperfusion injury,and inhibition of p38 MAPK signaling pathway can produce cardioprotection;isoflurane can produce cardioprotection by inhibition of p38 MAPK signaling pathway in the process of myocardial ischemia reperfusion injury.